Search

The Corona Virus Disease 2019 (COVID-19) pandemic has presented an unprecedented challenge globally. It is much bigger than a bio-medical concern now with the multitudes of socio-economic, socio-political, socio-cultural, and psycho-social impact, which are likely to outlast the pandemic itself by far and long. The pandemic and the resulting challenges across societies highlighted the existing social injustices in a neoliberal world for historically marginalized populations like homeless persons with mental illness (HPMI). The nationwide lockdown in India to resist the spread of the virus posed a unique challenge to this vulnerable population. The present study thus attempts to understand the experience of HPMI during the COVID-19 induced lockdown through the theoretical framework of social justice vis-à-vis injustice. Semi-structured interviews have been conducted on seven HPMI rehabilitated in the community through an NGO situated in Kolkata, India. Seven stakeholders have also been interviewed to understand their experience in providing services to the HPMI during the COVID-19 induced lockdown. Analyses of the narratives have been done using initial coding, focused coding and axial coding through the process of constant comparison of constructivist grounded theory (CGT) methodology. Critical insights from the study bring out experiences of HPMI during COVID-19 as a victim of structural violence, highlighting their exclusion and victimization due to the existing marginalized status, living closer to the edge as a consequence of the lockdown, lack of awareness of the gravity of the pandemic situation. The experiences of the stakeholders, on the other hand, pointed out the role of community members and social workers in partially mitigating the challenges. This study indicates that to mitigate the aftermaths, stakeholders, including community members, need to work together for rebuilding and enhancing the strength and resilience of the marginalized populations like HPMI, who are historically victims of social injustice in the neoliberal pandemic era.

Avalanche hotspot formation can severely limit the current handling capability of power devices. Trench field plate power MOSFETs can be prone to avalanche hotspots, especially in the termination regions. Subtle differences between the active and termination regions can result in current focalization into a small area of the termination and destruct the device. The avalanche hotspots are ascribed to kinks and negative differential resistance (NDR) branches in the termination diode I-V characteristics. In this work, we investigate the electrostatic origin of such features and propose the use of an integrated termination ballast to suppress the hotspot formation. An enhancement of ~3x in avalanche current capability is demonstrated through unclamped inductive switching (UIS) experiments.

Laryngeal paraganglioma is a rare tumor with diagnostic challenge. Many a times it can be confused with laryngeal cancers. CECT and MRI has an important role in its diagnosis. Surgical excision is the treatment of choice. Our case presented with stridor. Emergency tracheostomy was done followed by workup for surgery. Excision of the tumor was done by laryngeal fissure.

The most accurate estimation of transition probabilities for a multi-state model of health status requires longitudinal data. However, for many countries such data are usually not available. Instead, population level mortality incidence and disability prevalence rates are often all that can be accessed. In this paper, for a three-state no-recovery model (with states healthy, disabled, dead), using simple mathematical derivations, we propose a framework to estimate the age- and gender-specific boundaries within which each of the transition probabilities should fall. We then provide two methods for estimating unique transition probabilities—a least squares procedure and a method based on the ‘extra mortality’ factor proposed by Rickayzen and Walsh (Br Actuarial J 8(2):341–393, 2002, https://doi.org/10.1017/s1357321700003755 ). We also show the acceptable range for the ‘extra mortality’ factor given the mortality and disability data. Furthermore, we provide a critique of the method proposed by Van der Gaag et al. (Demogr Res 32:75, 2015), as their estimates can fall outside the acceptable boundaries. Finally, we estimate life and health expectancies, as well as premium rates for a life care annuity and a disability annuity using our derived transition probabilities.

Many commonly used compositional viscosity models require modeling parameters for an equation of state to make prediction. With the recent development of the Evangelista and Vargas correlations (Evangelista and Vargas, Fluid Phase Equilibria, 2018) that predict the critical properties for nonpolar hydrocarbons, a new methodology for predicting viscosities with simple volumetric or optical measurements performed at ambient conditions becomes feasible. Therefore, this study evaluated the proposed methodology on 13 pure components and 11 mixtures and found that their viscosities at various temperatures and pressures can be predicted with an AAPD of 10 and 8.9, respectively. The predictive capabilities of the proposed method are compared against those of current techniques, which require more input data. Our methodology offers predictive capability with a similar level of accuracy with the added benefit of significantly reducing the requirement of input data. The proposed approach uses simple laboratory tests only, which eliminated the need for laborious experiments such as composition analysis or viscosity measurements at high temperature and pressure, providing a significantly more viable option than existing techniques for viscosity estimation.

We examine the implications for Australian retirees of full access to dividend imputation credits using a stochastic life‐cycle model. We find that the availability of imputation credits can justify a significant bias towards Australian equities in retirement portfolios, largely at the expense of world equities. We also generate estimates of the value of imputation credits to retirees, finding it could potentially support increased consumption during retirement of 5–6 per cent, or equivalent value to a 8–9 per cent higher balance at retirement. Our study enhances the understanding of equity home bias, and provides insights relevant for public policy. [ABSTRACT FROM AUTHOR] email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims: Pecs block and its variations provides perioperative analgesia, reduce PONV and other opioid related side effects. We hypothesized that COMIBPES block in addition to general anaesthesia will provide better postoperative analgesia when compared to general anaesthesia alone in breast cancer surgery patients. Methods: After obtaining permission from the institutional review board and registering the trial with Clinical Trials Registry of India (CTRI), we conducted a double blinded randomized controlled trial of 100 patients posted for elective breast surgery with axillary dissection. Patients were divided into two groups, P (Pecs block) and C (control). Intraoperative analgesia, postoperative analgesia, postoperative nausea vomiting (PONV) and shoulder mobility on first postoperative day (POD1) were noted. Primary outcomes were the pain scores measured by visual analog scale (VAS) and cumulative intravenous morphine consumption from patient controlled analgesia (PCA) pump at measurement intervals of 0, 1, 4, 8, 12 and 24 hours postoperatively. Results: Intraoperatively, Group P patients did not require any additional analgesia, whereas all the patients in Group C required additional intraoperative morphine (mean, SD: 5.12, 2.63 mg, compared to nil in group P, P< 0.01). COMBIPECS block group had lower pain scores and PCA morphine requirements, less PONV and better shoulder mobility on POD1. Conclusion: COMBIPECS block is a valuable addition to general anaesthesia for breast cancer surgery as it reduces pain and PONV while allowing better postoperative shoulder mobility.

TPS5623 Background: Carboplatin-paclitaxel chemotherapy (with trastuzumab for HER2+ uterine serous carcinoma) is the standard of care first-line systemic treatment for recurrent or metastatic endometrial carcinoma (EC), which has a 5-year relative survival rate of only 17%. Worse survival outcomes have been shown for the mismatch repair deficient (dMMR) subtype of EC. Pembrolizumab (pembro), an anti-PD-1 antibody, showed compelling antitumor activity in previously treated, advanced MSI-H/dMMR EC in the phase 2 KEYNOTE-158 study (ORR, 48%; median duration of response [DOR], not reached; O’Malley JCO 2022). KEYNOTE-C93/GOG-3064/ENGOT-en15 (NCT05173987) is a phase 3, randomized, open-label study evaluating first-line pembro versus carboplatin-paclitaxel chemotherapy in patients with dMMR advanced or recurrent EC. Methods: Patients aged ≥18 years with histologically confirmed stage III/IV recurrent EC including carcinosarcoma (mixed Mullerian tumor), radiographically evaluable disease (measurable or nonmeasurable per RECIST v1.1), no prior systemic therapy (prior radiation with or without radiosensitizing chemotherapy > 2 weeks before first dose or prior hormonal therapy ≥1 week before randomization is permitted), and an ECOG PS ≤1 are eligible. Patients must have central confirmation of dMMR status. Approximately 350 patients will be randomized 1:1 to receive pembro 400 mg IV Q6W for 18 cycles (̃2 years) or carboplatin AUC 5 or 6 mg/mL/min IV Q3W and paclitaxel 175 mg/m2 IV Q3W for 6 cycles (with option for > 6 cycles). Trastuzumab is permitted for patients in the chemotherapy arm with HER2+ serous EC. Randomization is stratified by disease status (newly diagnosed advanced EC vs recurrent EC) and histology (endometrioid vs nonendometrioid). Treatment will continue for the specified number of cycles or until PD or unacceptable toxicity. Patients in the chemotherapy arm have the option to receive pembro following confirmed PD by blinded independent central review (BICR). Tumor imaging will be performed Q9W from randomization to week 54 and Q12W thereafter. AEs will be assessed from randomization to 30 days (90 days for serious AEs) after treatment discontinuation and graded per NCI CTCAE version 5.0. Dual primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints are ORR, disease control rate, and DOR per RECIST v1.1 by BICR; PFS per RECIST v1.1 by investigator review; PFS2 (ie, time from randomization to PD per investigator assessment or death from any cause after start of subsequent anticancer therapy); safety; and patient-reported outcomes. PFS and OS will be estimated by the Kaplan-Meier method, with treatment differences assessed by the stratified log-rank test and HRs with 95% CIs determined using a Cox proportional hazard model. Enrollment is ongoing. Clinical trial information: NCT05173987.

MicroRNAs (miRNAs) are non‐coding small RNAs that regulate gene expression at transcriptional and post‐transcriptional levels. The role of miRNAs in seed development and seed size/weight determination is poorly understood in legumes. In this study, we profiled miRNAs at seven successive stages of seed development in a small‐seeded and a large‐seeded chickpea cultivar via small RNA sequencing. In total, 113 known and 243 novel miRNAs were identified. Gene ontology analysis revealed the enrichment of seed/reproductive/post‐embryonic development and signaling pathways processes among the miRNA target genes. A large fraction of the target genes exhibited antagonistic correlation with miRNA expression. The sets of co‐expressed miRNAs showing differential expression between the two cultivars were recognized. Known transcription factor (TF) encoding genes involved in seed size/weight determination, including SPL, GRF, MYB, ARF, HAIKU1, SHB1, KLUH/CYP78A5, and E2Fb along with novel genes were found to be targeted by the predicted miRNAs. Differential expression analysis revealed higher transcript levels of members of SPL and REVOLUTA TF families and lower expression of their corresponding miRNAs in the large‐seeded cultivar. At least 19 miRNAs known to be involved in seed development or differentially expressed between small‐seeded and large‐seeded cultivars at late‐embryogenesis and/or mid‐maturation stages were located within known quantitative trait loci (QTLs) associated with seed size/weight determination. Moreover, 41 target genes of these miRNAs were also located within these QTLs. Altogether, we revealed important roles of miRNAs in seed development and identified candidate miRNAs and their target genes that have functional relevance in determining seed size/weight in chickpea.

BACKGROUND Dobutamine-atropine stress echocardiography (DSE) has lower sensitivity in patients with advanced liver disease (ALD) due to vasodilation. HYPOTHESIS Dopamine-atropine stress echocardiography (DopSE) may be an alternative to DSE in ALD patients by improving the blood pressure response to stress. METHODS The safety and tolerability of DSE and DopSE were compared in 10 volunteers. The safety, adverse effects, and efficacy of DopSE were then assessed in 105 patients, 98 of whom had ALD. Dopamine was infused in stepwise fashion from 5 µg/kg/min to a peak dose of 40 µg/kg/min. Atropine was given before and in early stages of dopamine infusion up to cumulative dose of 1.5 mg. The hemodynamic responses of 98 ALD patients were compared with 102 patients with ALD who underwent standard DSE. RESULTS In normal volunteers, systolic BP increased more with DopSE compared to DSE (61 ± 19 mm Hg vs 39 ± 15 mm Hg, P = .008). In 105 patients who underwent DopSE, none had adverse effects that required early stress termination. In the groups with ALD, the systolic BP increase (38 ± 28 mm Hg vs 12 ± 27 mm Hg, P

Background Our goal was to study the demographic, clinical and laboratory profile and outcome of scrub typhus-associated hemophagocytic lymphohistiocytosis (HLH) in the pediatric age group. Methods We conducted a prospective observational study in a tertiary care teaching hospital over a period of 1 year. Children in the age group of 1 month to 12 years with IgM ELISA positive for scrub typhus were included in the study. HLH was diagnosed using HLH-2004 criteria. Demographic, clinical and laboratory profile, treatment and outcome of HLH patients were noted and also compared with non-HLH scrub typhus patients. Results Among 58 children with scrub typhus infection, 18 had HLH. The mean age of patients with HLH was 35.3 ± 44.8 months and 61% were male. Anemia, thrombocytopenia and hyperferritinemia were seen in all the patients. Hypertriglyceridemia, hypofibrinogenemia and coagulopathy were noted in 78%, 56% and 44%, respectively. All the patients were treated with intravenous doxycycline for an average duration of 9.5 days. Intravenous immunoglobulin and methylprednisolone were given in 33% and 22% cases, respectively. Complications like acute respiratory distress syndrome (ARDS) (p = 0.001) and MODS (p = 0.004) were significantly high in the HLH group. Younger age ( 7 days, presence of convulsion, ARDS and MODS were the clinical predictors of scrub typhus-associated HLH. Conclusion HLH in scrub typhus infected children is being increasingly recognized. Younger age, prolonged fever, presence of convulsion, ARDS and MODS should alert clinicians of the risk of HLH. Treating the primary cause usually cures the disease and immunomodulator therapy need not be routinely administered.

Histone phosphorylation is a ubiquitous post-translational modification that allows eukaryotic cells to rapidly respond to environmental stimuli. Despite correlative evidence linking histone phosphorylation to changes in gene expression, establishing the causal role of this key epigenomic modification at diverse loci within native chromatin has been hampered by a lack of technologies enabling robust, locus-specific deposition of endogenous histone phosphorylation. To address this technological gap, here we build a programmable chromatin kinase, called dCas9-dMSK1, by directly fusing nuclease-null CRISPR/Cas9 to a hyperactive, truncated variant of the human MSK1 histone kinase. Targeting dCas9-dMSK1 to human promoters results in increased target histone phosphorylation and gene activation and demonstrates that hyperphosphorylation of histone H3 serine 28 (H3S28ph) in particular plays a causal role in the transactivation of human promoters. In addition, we uncover mediators of resistance to the BRAF V600E inhibitor PLX-4720 in human melanoma cells using genome-scale screening with dCas9-dMSK1. Collectively, our findings enable a facile way to reshape human chromatin using CRISPR/Cas9-based epigenome editing and further define the causal link between histone phosphorylation and human gene activation., Histone phosphorylation is a ubiquitous post-translational modification. Here the authors present a programmable chromatin kinase, dCas9-dMSK1, that enables controlled histone phosphorylation and specific gene activation.

Previous studies have shown that individuals with intellectual and developmental disabilities (IDD) have difficulty with decision making across a range of decision tasks and that their abilities and decision styles are linked to etiology or specific type of IDD. This chapter provides a comprehensive review of decision-making research involving adolescents and adults with IDD by examining key sources of difficulty emerging from the interplay of the basic processes of cognition, motivation, and emotion. Using the Pathways Model of Decision Processing as a guiding framework, the chapter also explores a range of personal and situational factors as possible explanations for observed differences, and limitations, in decision making by individuals with IDD. Viewing individual differences in decision making from a neurodevelopmental perspective, different pathways of decision processing are examined for likely utilization by individuals with various types of IDD to allow for a better understanding of how individual characteristics may influence decision functioning across different domains, including interpersonal and social situations. The chapter establishes a clear need for developing and evaluating effective approaches for strengthening the decision-making capabilities in individuals with IDD.

This article sets out principles and decision rules for setting appropriate drawdown and investment strategies during retirement given an individual’s objectives and risk tolerance. In particular, we highlight how the suitable drawdown strategy can relate to the objective, and how annuities might be combined with other investments to help manage risk. Our aim is to offer research-based guidance to product providers, financial advisers and individuals in formulating retirement strategies.